INTRODUCTION The dihydroorotate dehydrogenase (DHODH) inhibitors leflunomide and teriflunomide are immunomodulatory agents approved to treat rheumatoid arthritis (RA) and multiple sclerosis, respectively, and are actively being investigated as therapeutic agents for other immune-related diseases; however, both structurally related compounds have a number of potentially serious adverse effects. Vidofludimus, a new selective second-generation DHODH inhibitor, is chemically distinct from leflunomide/teriflunomide and appears to exhibit a distinct safety profile. OBJECTIVE The aim of the COMPONENT study was to assess the efficacy, safety, and pharmacokinetics of vidofludimus in the treatment of patients with active RA on a background therapy of methotrexate. This report focuses solely on the safety results of the COMPONENT trial. METHODS Patients received once-daily oral vidofludimus (N = 122) or placebo (N = 119) along with their standard of care methotrexate treatment for 13 weeks. Efficacy endpoints were assessed. Safety parameters were monitored throughout treatment and at follow-up. Plasma concentrations of vidofludimus were measured. RESULTS The primary efficacy endpoint, American College of Rheumatology 20 (ACR20) responder rate at 13 weeks, demonstrated numerical superiority in the treatment group compared with placebo; however, it did not reach statistical significance. Nonetheless, the COMPONENT study yielded important safety and pharmacokinetic data that could provide important information regarding the use of vidofludimus in other clinical trials, not only for RA but also for other autoimmune diseases. A safety profile for vidofludimus similar to placebo was obtained in this RA patient population. This includes similar rates of the adverse events of diarrhea, alopecia, neutropenia, and elevated liver enzymes, all of which are known drug-related adverse events reported for leflunomide and teriflunomide. A potential pharmacokinetic interaction between vidofludimus and methotrexate was observed. CONCLUSIONS Vidofludimus demonstrated a positive safety profile, making it a promising candidate for the treatment of a variety of immune-related diseases. TRIAL REGISTRATIONS ClinicalTrials.gov identifier: NCT01010581.

中文翻译：

---

活动性类风湿关节炎患者的选择性口服免疫调节剂Vidofludimus：COMPONENT研究的安全性结果。

简介二氢乳清酸脱氢酶（DHODH）抑制剂来氟米特和特氟米特是分别被批准用于治疗类风湿性关节炎（RA）和多发性硬化症的免疫调节剂，并且正在积极地研究其作为其他与免疫相关疾病的治疗剂。然而，两种结构上相关的化合物都有许多潜在的严重不利影响。Vidofludimus是一种新型的选择性第二代DHODH抑制剂，在化学上不同于来氟米特/ teriflunomide，并且似乎显示出独特的安全性。目的COMPONENT研究的目的是评估氨甲蝶呤背景治疗中氟哌丁草对活动性RA患者的疗效，安全性和药代动力学。本报告仅关注COMPONENT试验的安全性结果。方法患者接受每日一次口服氟尿嘧啶（N = 122）或安慰剂（N = 119）以及他们的标准甲氨蝶呤治疗，为期13周。评估疗效终点​​。在整个治疗过程中和随访时均监测安全性参数。测量了氟哌丁草的血浆浓度。结果主要疗效终点是美国风湿病学会20（ACR20）在13周时的应答率，与安慰剂相比，治疗组在数值上具有优势。但是，它没有达到统计学意义。尽管如此，COMPONENT研究仍提供了重要的安全性和药代动力学数据，这些数据可以为在其他临床试验中不仅在RA方面而且在其他自身免疫性疾病中使用氟哌丁草提供重要信息。在该RA患者人群中获得了与安慰剂相似的氟哌丁草安全性概况。这包括类似的腹泻，脱发，中性粒细胞减少和肝酶升高的不良事件发生率，所有这些都是已知的来氟米特和特立氟胺的药物相关不良事件。观察到氟哌丁草和甲氨蝶呤之间存在潜在的药代动力学相互作用。结论Vidofludimus表现出积极的安全性，使其成为治疗多种免疫相关疾病的有前途的候选药物。试验注册ClinicalTrials.gov标识符：NCT01010581。所有这些都是已知的来氟米特和特氟米特的药物相关不良事件。观察到氟哌丁草和甲氨蝶呤之间存在潜在的药代动力学相互作用。结论Vidofludimus表现出积极的安全性，使其成为治疗多种免疫相关疾病的有前途的候选药物。试验注册ClinicalTrials.gov标识符：NCT01010581。所有这些都是已知的来氟米特和特氟米特的药物相关不良事件。观察到氟哌丁草和甲氨蝶呤之间存在潜在的药代动力学相互作用。结论Vidofludimus表现出积极的安全性，使其成为治疗多种免疫相关疾病的有前途的候选药物。试验注册ClinicalTrials.gov标识符：NCT01010581。